Malaligned teeth play a major role in the etiology and progression of periodontal disease. Patient have difficulty practicing adequate oral hygiene in areas where teeth are crowded and rotated. Root proximity with accompanying into thin interdental bone are detrimental to long-term periodontal status. Traumatic occlusion, a result of interarach dental or skeletal discrepancies, weakens the periodontium. By treating the malocclusion of a periodontally-compromised patient, the prognosis of the dental health is enhanced, since the treatment is targeted at the etiologic agent of the progressive bone loss. A firm periodontal foundation must be present prior to initiation of orthodontic tooth movement. Regeneration of the original periodontium reduces the risk of detrimental bone loss as a result of orthodontic tooth movement and enhances the stability of a orthodontically-positioned dentition. The combination of platelet-derived growth factor and insulin-like growth factor have been shown to potentiate healing of both hard and soft tissue. Complementary effects of these two growth factors occur in mitogenesis, cell metabolism, and cell migration. The synergistic properties of the PDGF/IGF-I interaction during the healing of periodontal defects have been explored intensively in beagle dog studies. The proposed study will elucidate the effects of orthodontic tooth movement on periodontium regenerated by means of a polypeptide growth factors. As a first aim, a pilot study will be completed to evaluate the regeneration of the periodontium about beagle teeth with naturally occurring disease. Following regeneration, orthodontic movement of the dentition will be performed. Histological examination of the response of the regenerated tissue to the movement will be conducted; and a comparison to the response found in healthy dentition subjected to orthodontic tooth movement will be completed. AIM 2 will consist of evaluating the pattern of regeneration and the response to orthodontic movement by longitudinal radiographs. Sequential standardized radiography will determine the millimeter amount of regeneration and maintenance or loss of these calcified tissues as tooth movement progresses. AIM 3 will involve assaying for tissue markers characteristic of orthodontic tooth movement and periodontium regeneration. This markers include Type I, III, XII collagen, ostecalcin, alkaline phosphatase, and acid phosphatase. The data collected will be used to explore the benefits and limitations of periodontium regeneration in conjunction with orthodontic tooth movement. KEYWORDS: Periodontium, Regeneration, Orthodontic tooth movement, Beagle dog, Platelet-derived growth factor, Insulin-like growth factor